Visceral hyperalgesia in children with functional abdominal pain.

OBJECTIVE: Our purpose was to evaluate visceral sensitivity and psychologic profiles in children with functional gastrointestinal disorders. STUDY DESIGN: We measured visceral perception in the stomach and in the rectum by using an electronic barostat. Psychologic questionnaires were completed. Ten children with recurrent abdominal pain (RAP)(8 female, mean age 11.3 +/- 0.8 years), 10 children with irritable bowel syndrome (IBS) (8 female, mean age 13.0 +/- 0.9 years), and 15 control children (8 female, mean age 12.7 +/- 1.2 years) completed the study. RESULTS: Thresholds for visceral perception in the rectum were decreased in patients with IBS (P <.001 vs control patients) and in patients with RAP (P <.05 vs control patients). Children with IBS had lower thresholds than children with RAP (P <.01). In contrast, thresholds for perception were decreased in the stomach of children with RAP (P <.005 vs control patients) but not in children with IBS. There were elevated anxiety scores in 45% of patients. Duration of symptoms was associated with higher scores of anxiety (P <.001) and depression (P <.02). CONCLUSIONS: Hyperalgesia was demonstrated in children with RAP and IBS; sites of hyperalgesia appear to be associated with different symptom phenotypes; anxiety was common, and there was an association between the duration of symptoms and increased scores for both anxiety and depression.

Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease.

BACKGROUND: Bacteremia occurs frequently after intestinal transplantation (ITx) in children. During our initial experience with this procedure, we noted that bacteremic episodes tended to occur simultaneously with the presence of rejection and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD). AIM: To document the association of bacteremia with rejection and GI PTLD in pediatric ITx recipients. METHODS: Retrospective analysis of all medical records from 62 children who underwent ITx between July 1990 and January 1998 at Children's Hospital of Pittsburgh. A bacteremic episode was defined as two positive blood cultures from different sites at the same time or from the same site at different times. Rejection and PTLD were defined using previously published criteria. RESULTS: A total of 39/62 ITx recipients had 133 blood stream infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of fungemia. Enteric organisms were the most frequently recovered pathogens (Gram negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a single organism (n=57), with another enteric bacteria (n=23), or with coagulase negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on 21 occasions. An obvious source of bacteremia was not found for 115/121 episodes. Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in combination with CONS were recovered on 63/107 occasions, although CONS were recovered alone only 11 times. CONCLUSIONS: Bacteremia accompanies GI rejection and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect the allograft when bacteremia occurs without an obvious source in these patients. This is especially true for patients with bacteremia due to enteric organisms.

The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children.

OBJECTIVES: Eosinophilic esophagitis, previously confused with esophageal inflammation due to gastroesophageal reflux, has recently begun to be distinguished from it. We undertook this analysis of our large series of children with the condition to clarify its spectrum: its presenting symptoms; its relation to allergy, respiratory disease, and reflux; its endoscopic and histological findings; and its diagnosis and therapy. METHODS: We analyzed the details of our clinical series of 30 children with eosinophilic esophagitis, defining it as > or =5 eosinophils per high power field in the distal esophageal epithelium. Retrospective chart review was supplemented by prospective, blinded, duplicate quantitative evaluation of histology specimens, and by telephone contact with some families to clarify subsequent course. Presentation and analysis of the series as a whole is preceded by a case illustrating a typical presentation with dysphagia and recurrent esophageal food impactions. RESULTS: Presenting symptoms encompass vomiting, pain, and dysphagia (some with impactions or strictures). Allergy, particularly food allergy, is an associated finding in most patients, and many have concomitant asthma or other chronic respiratory disease. A subtle granularity with furrows or rings is newly identified as the endoscopic herald of histological eosinophilic esophagitis. Histological characteristics include peripapillary or juxtaluminal eosinophil clustering in certain cases. Association with eosinophilic gastroenteritis occurs, but is not common. Differentiation from gastroesophageal reflux disease is approached by analyzing eosinophil density and response to therapeutic trials. Therapy encompasses dietary elimination and anti-inflammatory pharmacotherapy. CONCLUSION: Awareness of the spectrum of eosinophilic esophagitis should promote optimal diagnosis and treatment of this elusive entity, both in children and in adults.

Immunoreactive trypsinogen levels in pediatric patients with intestinal failure awaiting intestinal transplantation.

The aim of this study was to evaluate pancreatic function in total parenteral nutrition (TPN)-dependent children with permanent intestinal failure by measuring immunoreactive trypsinogen (IRT) levels. Between 1992 and 1996, 105 pediatric patients with permanent intestinal failure were referred to the Children's Hospital of Pittsburgh for small intestinal transplant evaluation. Serum samples were available from 55 of them. Ten suffered from intestinal pseudo-obstruction or microvillus inclusion disease, while 45 had short bowel syndrome (SBS). IRT levels were significantly higher (p < 0.001) in SBS patients (89.4 +/- 9.2 ng mL) compared to controls (43.4 +/- 5.6 ng/ nL) without liver, gastrointestinal, or kidney disease. IRT levels did not correlate with liver injury, length of bowel, or the cause of SBS. Five of 20 patients who underwent intestinal transplantation developed pancreatitis during a median post-operative follow up 15.4 months later. IRT levels failed to predict who would develop pancreatitis post-transplant. The data suggest that elevated plasma IRT levels are common among children with intestinal failure, but fail to identify patients at risk for pancreatitis post-transplant.

Intestinal transplantation in children with chronic intestinal pseudo-obstruction.

BACKGROUND: Children with chronic intestinal pseudo-obstruction (CIPO) often require total parenteral nutrition (TPN) which puts them at risk of liver failure and recurrent line infections. Intestinal transplantation has become a therapeutic option for TPN dependent children with intestinal failure who are failing management with TPN. AIMS: To investigate the outcome of children with CIPO referred for intestinal transplantation. METHODS: A retrospective review was carried out of records and diagnostic studies from 27 patients with CIPO referred for intestinal transplantation. RESULTS: Five children were not listed for transplantation: two because of parental decision, two because of suspicion of Munchausen syndrome by proxy, and one because he tolerated enteral nutrition. Six are still TPN dependent and awaiting transplantation. Eight children died awaiting transplantation. Eight children underwent transplantation. Three died (two months, seven months, and four years after transplant). Five children are alive with a median follow up of 2.6 years (range two months to six years). All transplanted children were able to tolerate full enteral feedings. The postoperative course was complicated by dumping syndrome, Munchausen syndrome by proxy, narcotic withdrawal, and uncovering of achalasia. Conclusion-Intestinal transplantation may be a life saving procedure in children with CIPO. Early referral and thorough pretransplant evaluation are keys to successful transplantation.

Factors impacting the survival of children with intestinal failure referred for intestinal transplantation.

PURPOSE: The aim of this study was to analyze factors impacting on the survival of pediatric patients with intestinal failure referred for intestinal transplantation (ITx). METHODS: Two hundred fifty-seven children (mean age, 3.4+/-0.26 years) with intestinal failure were evaluated for ITx between 1990 and 1998. All patients were dependent on total parenteral nutrition (TPN) for a mean of 31+/-2.7 months. The mean follow-up time from the date of evaluation was 9.2+/-0.9 months. RESULTS: Eighty-two (32%) children underwent ITx with a mean waiting time of 10.1+/-1.3 months (simultaneous liver-intestinal allograft in 68% instances). Of the 175 patients who did not undergo transplantation, 120 died, 23 were lost to follow-up, and 32 are alive. Younger patients (< or =1 year) had poorer survival rates than patients older than 1 year (P<.0001). The patients with the worse prognosis were those with necrotizing enterocolitis, and those with the best prognosis were those with Hirschsprung's disease. Patients with "surgical" causes had poorer survival rates than those with "nonsurgical" causes (P<.04). Patients with bridging fibrosis or established cirrhosis had an earlier mortality than patients with portal fibrosis (P<.003). The worst survival rate was found for patients with bilirubin levels of greater than 3 mg/dL (P<.0001), plateletcounts less than 100.000/mL (P<.0001), prothrombin time greater than 15 seconds (P = .03) or partial thromboplastin time greater than 40 seconds (P<.04). Children who at the time of evaluation needed only an isolated intestinal allograft had a better prognosis than those who required a combined liver-intestine allograft (P<.00001). With multivariate analysis independent prognosis risk factors of poor outcome were hyperbilirubinemia and severity of histopathologic damage. CONCLUSIONS: Early referral for ITx should occur before the development of liver dysfunction, taking into consideration the aforementioned risk factors that would facilitate the development and ominous evolution to liver failure.

Intestinal transplantation in children.

Intestinal transplantation has emerged in the last decade as a lifesaving procedure for patients with intestinal failure who are suffering from complications arising from the administration of total parenteral nutrition. Indications for transplantation include irreversible liver injury and loss of vascular access. At least 50 children in the United States may benefit from intestinal transplantation every year. In this article, indications, pre- and postoperative management, and outcomes of intestinal transplantation in children are discussed.

Anatomic variability of rejection in intestinal allografts after pediatric intestinal transplantation.

BACKGROUND: Rejection of the allograft is a major contributor to morbidity and mortality in children who undergo a small intestinal transplant. Operational definitions for histologic rejection have been established, but little is known about the anatomic variability of the histologic abnormalities. STUDY DESIGN: Biopsy reports were reviewed retrospectively from more than 1200 endoscopies performed on the 41 children who received intestinal transplantation between 1990 and 1995. RESULTS: Biopsies were performed in the proximal jejunum and distal ileum allograft simultaneously on 248 occasions. In 168 biopsies, neither site was histologically abnormal; in 80, rejection was found. In 42, both regions were abnormal; however, in 17 only the jejunum was involved and in 21 the rejection exclusively involved the ileum. Among children whose allograft included colon, rejection was absent in colon and ileum in 34 biopsies, involved both in 6, involved ileum but not colon in another 6 and involved colon but not ileum in only one. When the allograft included stomach, rejection was absent in the stomach and jejunum 39 times, involved both sites 8 times, involved jejunum and not the stomach 10 times, but involved the stomach and not jejunum only once. Endoscopic appearance correctly predicted histologic rejection 63% of the time. CONCLUSION: Anatomic variability may exist in the rejection process. Sampling the jejunum and ileum seems to have similar sensitivity in detecting rejection, whereas sampling stomach and the colon is less sensitive. When allograft rejection is suspected on clinical grounds, sampling more than one area of the graft may be necessary for histologic confirmation.

[Neonatal hemochromatosis]. / Neonatal hemokromatose.

Neonatal haemochromatosis is a disorder which affects foetuses and newborns. It is characterized by hepatocellular insufficiency, often appearing on the first day of life in the form of coagulopathy, hypoalbuminemia, hypoglycemia and jaundice. While spontaneous recovery has been reported, most of these infants die, and the diagnosis was previously often made during autopsy. With the help of MRI and salivary gland biopsies, plus increasing awareness of this disorder, the diagnosis is now often made quite early, and successful liver transplantations have been reported. Recently, there have also been encouraging preliminary reports of successful intervention with antioxidant and chelation pharmacotherapy, using a combination of selenium, vitamin E, N-acetylcysteine, deferoxamine, and prostaglandin E. We describe two patients with neonatal haemochromatosis who were both treated with this new "cocktail", one of whom died at five days of age, while the other survived, but needed a liver transplant at 2 1/2 months of age. The pathology of this condition is characterized by hepatic cirrhosis with giant cell transformation, and by siderosis of extrahepatic tissues. The prognosis is poor, and our experience with antioxidant treatment has been disappointing. Liver transplantation is a therapeutic option, but its use is limited by the scarcity of donor organs and the small size of many of the patients.

Endoscopies in pediatric small intestinal transplant recipients: five years experience.

OBJECTIVE: Intestinal transplantation has become an option as a treatment for permanent intestinal failure. Endoscopy is an essential tool in assessing the intestinal allograft after intestinal transplantation. The aim of this study was to analyze our experience using endoscopy in intestinal transplant recipients. METHODS: This was a retrospective review of endoscopic and histological reports in 41 children who received an intestinal transplant between 1990 and 1995 at Children's Hospital of Pittsburgh. RESULTS: A total of 1273 endoscopies was performed of which 760 were ileoscopies via allograft ileostomy, 273 were upper endoscopies, and 240 were colonoscopies. One hundred four rejection episodes were documented histologically in 32 patients, 6 days to >4 yr after transplantation. Most episodes were mild and easily treated with increased immunosuppression; however, severe rejection with mucosal exfoliation was seen in nine patients. Rejection sometimes involved only part of the allograft. Endoscopic appearance alone without biopsies was sensitive enough to diagnose only 63% of the rejection episodes. Epstein-Barr and cytomegalovirus infections occurred in 11 and eight patients, respectively, and involved both native bowel and allograft in some. Complications of endoscopy were few: one perforation, three episodes of bleeding, and three episodes of transient respiratory compromise. CONCLUSIONS: Endoscopy is an essential tool in the postoperative assessment of intestinal transplant recipients. Frequent surveillance ileoscopies with biopsies should be performed after transplantation. If patients clinically deteriorate with fever, diarrhea, bacteremia, or gastrointestinal bleeding and a clear cause is not elucidated by ileoscopy, an upper endoscopy with biopsies is indicated.

Neonatal hemochromatosis: outcomes of pharmacologic and surgical therapies.

BACKGROUND: Neonatal hemochromatosis (NH), also known as perinatal hemochromatosis or neonatal iron storage disease, is a disorder in fetuses and newborn infants. A retrospective study was conducted to report management of patients with NH. METHODS: Retrospective analysis was conducted by chart review and by review of histologic material from patients with NH. RESULTS: Neonatal hemochromatosis was diagnosed in 14 patients between 1985 and 1995. All were considered for orthotopic liver transplantation (OLTX). From 1993 onward, all patients were treated with an antioxidant-chelation "cocktail," consisting of deferoxamine, vitamin E, N-acetylcysteine, selenium, and prostaglandin-E1. Of 6 patients with NH diagnosed before 1993, 4 underwent OLTX; only 1 is still alive. Of 8 patients with NH diagnosed after 1993 and treated with the cocktail, 7 expired before OLTX. One stabilized on therapy, but having never recovered full synthetic liver function, underwent OLTX and is now alive and well. CONCLUSION: Neonatal hemochromatosis carries a grim prognosis; however, successful OLTX is curative. The use of an antioxidant-chelation cocktail did not improve outcome in the patients studied. Earlier (perinatal) diagnosis may be required for optimal results. Further study of other interventions, including antenatal diagnosis and earlier institution or modification of cocktail therapy appears warranted.

Serial measurement of Epstein-Barr viral load in peripheral blood in pediatric liver transplant recipients during treatment for posttransplant lymphoproliferative disease.

BACKGROUND: Few data are available describing the natural history of the Epstein-Barr virus (EBV) viral load after the diagnosis of EBV-associated posttransplant lymphoproliferative disease (PTLD). Accordingly, we prospectively followed the EBV viral load after the diagnosis of EBV/PTLD in seven pediatric orthotopic liver transplant recipients. METHODS: EBV viral loads were serially measured by quantitative competitive polymerase chain reaction of the peripheral blood from pediatric patients with PTLD and correlated with the clinical course of these children. Viral loads >200 genome copies/10(5) peripheral blood lymphocytes were considered consistent with an increased risk of PTLD. Viral loads <200 obtained during treatment for PTLD were considered evidence of "clearance" of EBV; subsequent loads >200 were considered evidence of virologic "rebound." RESULTS: The mean EBV viral load at the time of diagnosis of PTLD was 1029. All patients "cleared" their EBV viral load during the treatment of PTLD; patient and graft survival in this series was 100%. The mean time to clearance of EBV from the peripheral blood (18.8 days) was similar to the mean time to onset of first rejection (13.8 days). EBV viral load at the time of diagnosis of rejection after PTLD was always <100. A rebound in the EBV viral load to >200 was noted in five of seven patients a median of 3.5 months (range 2.3-13 months) after the diagnosis of EBV/PTLD. However, none of these children has had any evidence of PTLD recurrence. CONCLUSIONS: Clearance of the EBV viral load from the peripheral blood seems to correlate with restoration of the host's immune response as noted both by the regression of the PTLD and the onset of rejection. Late rebound of the EBV viral load is common and does not seem to predict disease recurrence.

Postviral gastroparesis: presentation, treatment, and outcome.

We describe the clinical features and long-term outcome of 11 children who had persistent gastroparesis after an acute viral illness, eight of whom tested positive for rotavirus. Gastric emptying was delayed in the 10 children evaluated with scintigraphy. Antroduodenal manometry confirmed postprandial antral hypomotility in 10 subjects. All children recovered within 6 to 24 months.